Submission Details
Molecule(s):
C=CC(=O)N1CCCC(c2nc3ccccc3s2)C1
O=C(C(F)Cl)N1CCCC(c2nc3ccccc3s2)C1
CC#CC(=O)N1CCCC(c2nc3ccccc3s2)C1
Design Rationale:
Fragment 0749 is excellently oriented to accommodate these alternative warheads for covalently binding fragments. As suggested by others on the forum, acrylamide (as in ibrutinib), chlorofluoroacetamide and propiolamide warheads (as in acalabrutinib) are less reactive and more drug like than the original chloracetamide warhead of 0749. This is my follow-up attempt to make designs incorporating these warheads. #covalent